1. Field of the Invention
The present invention relates to an apparatus and method for detecting biomolecular bonding. More particularly, the present invention relates to an apparatus and method for detecting whether biomolecular bonding has been achieved, by monitoring frequency change before and after the biomolecular bonding.
2. Description of the Related Art
A biochip refers to a biological microchip comprising biomolecules such as deoxyribonucleic acid (DNA) sequences, DNA segments, ribonucleic acid (RNA) sequences, peptides and/or protein molecules which are immobilized at intervals on a small solid substrate. A biochip enables analysis of gene expression, genetic mutation, biomolecule defects, protein distribution, and like characteristics of an experimental sample. The substrate can be made, for example, of glass or silicon. A biomolecule immobilized on the surface of the biochip can function as a probe that searches molecular information included in an experimental sample. By mixing the biochip with an experimental sample to be analyzed, substances in the sample can bind with a probe fixed on the biochip surface. By detecting and analyzing the binding, information can be obtained on the substances in the experimental sample.
In order to determine whether an experimental sample includes a biomolecule capable of bonding with a probe biomolecule, a detection system is needed to detect bonding between the probe biomolecule and the sample biomolecule.
Existing signal detecting methods include, for example, a laser-induced fluorescence (LIF) detecting method, an electrochemical detecting method, or a mechanical detecting method. FIGS. 1A to 1D illustrate examples of conventional bio-bonding detecting systems and methods.
FIG. 1A is a view illustrating a conventional LIF detecting method. The LIF detecting method includes labeling a sample biomolecule with a fluorescent material. The sample biomolecule with the fluorescent label is mixed with the probe biomolecules, and any binding between the probe biomolecule and the sample biomolecule is determined optically with a confocal microscope or a charge coupled device (CCD) camera. This method, however, requires a pre-processing reaction for binding the fluorescent material to the sample biomolecule before the bonding reaction between the probe and the sample biomolecule, possibly causing loss or contamination of the sample biomolecule. Another disadvantage includes the requirement for a complicated, high-priced optical reader system to read the result of the bonding reaction between the probe biomolecules and the sample biomolecule. Additionally, the optical detection method makes it difficult to provide a compact sized optical detector, and a digitized output cannot be obtained.
FIG. 1B is a view of a conventional mechanical detector. The mechanical detecting method uses a micro-assembled cantilever to monitor intermolecular binding force before and after the bonding between the probe biomolecules and the sample biomolecule. However, this method requires precise monitoring of the deflection of the cantilever beam. Additionally, an instrument such as a laser or the like is also required.
FIGS. 1C and 1D each illustrate a conventional biomolecular-bonding detecting apparatus using a capacitance device. Specifically, FIG. C illustrates a biomolecular-bonding detecting apparatus using a trench-type capacitance device, and FIG. 1D illustrates a biomolecular-bonding detecting apparatus using a planar capacitance device.
In the case of detecting biomolecular-bonding using a capacitance device, there is a disadvantage in that it is difficult to form a compact-sized capacitance device. Since capacitance is proportional to cross-sectional area and is inversely proportional to thickness, a capacitance device is difficult to design to facilitate bio processing, since the cross-sectional area must be increased. In a biomolecular-bonding detecting apparatus using a trench-type capacitor as in FIG. 1C, a deep trench is formed so as to make the capacitor thinner and to enlarge the cross-sectional area thereof. In this case, however, there is a disadvantage in that the actual gap is very small, thus making it difficult to implement bio-processing. The biomolecular-bonding detecting apparatus of FIG. 1D using a capacitor similar to that formed as a comb shape in a plane, also has a disadvantage in that the thickness of a metallic thin film is so small that many capacitance devices cannot easily be formed on a metallic film, thereby resulting in poor sensitivity in detecting biomolecular-bonding between molecules.